Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was >20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI
Results. In the CIA model of arthritis, MSCs did not confer any benefit. Both the clinical and the immunologic findings suggested that MSCs were associated with accentuation of the Th1 response. Using luciferaseexpressing MSCs, we were unable to detect labeled cells in the articular environment of the knee, suggesting that worsening of the symptoms was unlikely due to the homing of MSCs in the joints. Experiments in vitro showed that the addition of TNF␣ was sufficient to reverse the immunosuppressive effect of MSCs on T cell proliferation, and this observation was associated with an increase in interleukin-6 secretion.Conclusion. Our data suggest that environmental parameters, in particular those related to inflammation, may influence the immunosuppressive properties of MSCs.
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